磷酸二酯酶4抑制剂治疗银屑病的研究进展

Research progress on phosphodiesterase 4 inhibitors in treatment of psoriasis

银屑病是一种遗传和环境共同作用诱发的、免疫介导的慢性炎症性皮肤病。环磷酸腺苷(cAMP)/蛋白激酶A(PKA)通路与银屑病的发病机制密切相关,而磷酸二酯酶4是可以专一水解cAMP的酶,因此磷酸二酯酶4成为银屑病治疗的期望小分子靶点。磷酸二酯酶4抑制剂类药物通过竞争性阻断磷酸二酯酶4对cAMP的降解作用,使T辅助细胞1(Th1)、Th2和Th17的免疫反应减弱来发挥治疗作用。磷酸二酯酶4抑制剂如阿普司特、罗氟司特、克立硼罗、Hemay005、奥利司特、MK-0873、tanimilast、DRM02在治疗银屑病及其共病方面有巨大的潜力。就磷酸二酯酶4抑制剂治疗银屑病的作用机制、疗效、安全性进行了总结。

Psoriasis is an immune-mediated chronic inflammatory skin disease induced by a combination of genetics and the environment.cAMP/PKA pathway is closely related to the pathogenesis of psoriasis,and phosphodiesterase 4 is an enzyme that can specifically hydrolyze cAMP,so phosphodiesterase 4 becomes desired small molecule targets for psoriasis therapy.Phosphodiesterase 4 inhibitor drugs play a therapeutic role by competitively blocking the degradation of cAMP by phosphodiesterase 4,then weakening the immune response of Th1,Th2,and Th-17.Phosphodiesterase 4 inhibitor drugs,such as apremilast,roflumilast,criborrol,Hemay005,orlistat,MK-0873,tanimilast,and DRM02 have great potential in the treatment of psoriasis and its comorbidities.This article summarizes the mechanism of action,efficacy,and safety of phosphodiesterase 4 inhibitor drugs in treatment of psoriasis.